Internal free magnesium modulates the voltage dependence of contraction and Ca transient in rabbit ventricular myocytes.
We investigated the effect of altering internal free magnesium concentration (Mgi) on the contraction and Cai transient of patch-clamped rabbit ventricular myocytes. Experiments were performed at 35 degrees C; cells were held at -40 mV to inactivate Na channels and T-type Ca channels, and at this potential (and in the absence of cyclic AMP) "Ca-induced Ca release" is the primary trigger mechanism. Cells dialysed with a low Mgi (2.9 muM) had a large and fast phasic contraction and Cai transient at positive potentials (+60, +80 mV). Cells dialysed with a high Mgi (7.1 mM) had a small or absent phasic contraction and Cai transient at positive potentials. These effects were due to a change in free Mgi, and not due to a change in [Mg.ATP]. In cells dialysed with a low Mgi, application of Ca channel blockers (32 muM nifedipine with 10 muM D600) for a single beat abolished current through L-type Ca channels (ICa,L); however, 53% of the Cai transient was still elicited. Adding 5 mM Ni to Ca channel blockers abolished the remaining Cai transient, indicating that (in the absence of ICa,L) the transient might be triggered by reverse Na/Ca exchange. In cells dialysed with a high Mgi, a single-beat switch to Ca channel blockers was sufficient alone to abolish the Cai transient, indicating that under these conditions Ca entry via ICa,L is the primary sarcoplasmic reticulum trigger mechanism. These results suggest that raised free Mgi might partially inhibit the activity of the Na/Ca exchange, or might limit its ability to trigger Ca release.
Howarth
F C
FC
Department of Physiology, Worsley Medical and Dental Building, University of Leeds, Leeds, LS2 9NQ, UK.
Levi
A J
AJ
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology; D013997:Time Factors
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015222:Sodium Channels; D012964:Sodium; D008274:Magnesium; D002118:Calcium